Endothelin 1 (ET-1) is a potent vasoconstrictor peptide possibly involved in the pathophysiology of essential hypertension. We sought to determine whether the contribution of ET-1 to the regulation of basal vascular tone is increased in hypertensive patients (HTs). To this purpose, we compared the effect of intraarterial infusion of an ET/A-receptor blocker (BQ-123, 100 nmol/min for 60 min), alone and in combination with an ET/B-receptor blocker (BQ-788; 50 nmol/min for 60 min) in 7 normotensives (NTs) and 7 HTs. BQ-123 did not significantly change forearm blood flow (FBF; strain-gauge plethysmography) in NTs (2.6+/-0.4 before vs 2.5+/-0.7 mL/min/dL after BQ-123; P=0.50), but significantly increased FBF in HTs (from 2.9+/-1.3 at baseline to 4+/- 1.5 mL/min/dL; P<0.02). The addition of BQ-788 to BQ-123 infusion did not induce any significant change in FBF in NTs (2.4+/-0.9 mL/min/dL; P=0.71 vs BQ-123 alone), but produced an additional, though not significant, increase in FBF in HTs (to 5+/-1.7 mL/min/dL; P= 0.37 vs BQ-123 alone). To investigate the possibility of a different reactivity of vascular smooth muscle cells to ET-1, we compared the effect of exogenous ET-1 in NTs and HTs. ET-1 infusion (5 pmol/min for 60 min) significantly decreased FBF in both NTs (from 2.6+/-0.8 at baseline to 1.5+/-0.4 mL/min/dL; P<0.004) and in HTs (from 2.6+/-0.5 to 1.3+/-0.5 mL/min/dL; P<0.001), without significant difference between the 2 groups (P=0.31). These findings suggest an enhanced vasoconstrictor activity of ET-1 in HTs. This effect is not related to a greater sensitivity of the microvasculature to ET-1, but likely reflects increased local availability of the peptide.